Transcranial Direct Current Stimulation for the Treatment of Deficits After Traumatic Brain Injury

Our long-term goal is to develop safe and effective treatments for symptoms of mild to
moderate TBI (mmTBI) that restore patients to higher levels of functioning, decrease
disability, and promote brain healing. The objective of this application is to investigate
the use of transcranial direct current stimulation (tDCS) to treat symptoms of executive
dysfunction and depression in patients with mmTBI. Our central hypotheses are (1) tDCS paired
with relevant cognitive training facilitates improves executive function on National
Institutes of Health (NIH)-approved neuropsychological measures, (2) tDCS reduces depression
scores on NIH Common Data Elements for TBI, (3) that these improvements in emotion and
cognition will be detectable up to one year after stimulation, and (4) certain clinical
variables will reliably predict response to tDCS. These objectives were formulated based on
our clinical experience with Dr. Ronald Yeo (project mentor) characterizing symptomatic
patients with mmTBI in the post-acute setting and groundbreaking research led by Dr. Vincent
Clark (project mentor) that has demonstrated robust increases in attention and learning with
tDCS.

Specific Aim 1: tDCS for executive dysfunction in mmTBI Experiments in this aim will test the
hypothesis that in patients with mmTBI, left prefrontal anodal tDCS concurrent with cognitive
training for ten consecutive weekdays will result in significantly more improvement in
executive function compared to sham stimulation. Patients with cognitive complaints 3 months
to 2 years after mmTBI will be recruited from local emergency departments and brain injury
clinics. Aim 1.1: tDCS will be paired with computer-based cognitive training tasks of
response inhibition, set shifting, and working memory, while executive function will be
measured with the NIH Examiner battery before, immediately after, and one month after
stimulation. Aim 1.2: Persistence of post-traumatic symptom reduction and quality of life
improvement will be assessed with Common Data Elements instruments via telephone interview at
6 months and one year. Aim 1.3: Clinical predictors of tDCS response including injury
severity, premorbid intelligence, and post-traumatic symptom burden will be determined with
linear mixed-models analysis.

Specific Aim 2: tDCS for depressive symptoms in mmTBI Experiments in this aim will test the
hypothesis that left prefrontal anodal tDCS in patients with mmTBI will significantly reduce
depressive symptoms compared to sham stimulation. Aim 2.1: Patients will be assessed for
symptoms of depression via self-report instruments and clinician-administered scales from NIH
Common Data Elements before, immediately after, and one month after the stimulation protocol.
Aim 2.2: Persistence of antidepressant benefit will be assessed via telephone interview at 6
months and one year. Aim 2.3: clinical predictors of tDCS response such as injury severity,
premorbid intelligence, and symptom burden will be determined.

Inclusion Criteria:

1. aged 18-55

2. TBI with + loss of consciousness (LOC) less than 24 hours

3. injured between 3 months and 5 years ago

4. Glasgow Coma Score (GCS) between 9 and 15 upon emergency department (ED) admission

5. less than 1 week of post-traumatic amnesia (PTA)

6. 1 out of 4 cognitive symptoms on the Neurobehavioral Symptom Inventory (NSI)

Exclusion Criteria:

1. history of neurological disease or seizures

2. history of psychosis

3. history of recent substance dependence (past 2 years)

4. any skull defect

5. presence of any implanted electrical device

6. recent medical instability (within 3 weeks)

7. pregnancy

8. appointment of a legal representative.